Analysis of drug resistance marker genes of Plasmodium falciparum after implementation of artemisinin-based combination therapy in Pune district, India
The global emergence and spread of malaria parasites resistant to antimalarial drugs is a major problem inmalaria control and elimination. In this study, samples from Pune district were characterized to determineprevalence of molecular markers of resistance to chloroquine (pfcrt codons C72S, M74I, N75E, K76T andpfmdr-1 N86Y, Y184F), pyrimethamine (pfdhfr C50R, N51I, C59R, S108N), sulfadoxine (pfdhps, S436A,A437G, K540E, A581G), and artemisinin (pfkelch13, C580Y, R539T). The pfcrt K76T mutation was found in78% samples as CVMNT, SVMNT and CVIET haplotype. The pfmdr-1 N86Y and Y184F mutations werefound in 54% of samples. The pfdhfr double mutation C59R + S108N was present in 67% of samples, whilethe pfdhfr triple mutation (N51I + C59R + S108N) was not detected. The pfdhps mutations A437G andK540E were found in 67% of samples. Single mutants of pfdhps were rare, with K540E detected in only 6patient samples. Similarly, pfdhps A581G was found in 13 of the isolates. The molecular markers associatedwith artemisinin resistance (mutations in pfkelch13 C580Y, R539T) were not detected in any of the isolates.These results suggest an emerging problem with multidrug-resistant P. falciparum. Though the genotypeconventionally associated with artemisinin resistance was not observed, chloroquine-resistant genotype hasreached complete fixation in the population. Moreover, the prevalence of mutations in both pfdhfr and pfdhps,with the presence of the quadruple mutant, indicates that continued monitoring is required to assess whethersulfadoxine-pyrimethamine can be used efficiently as a partner drug for artemisinin for the treatment of P.falciparum.
Volume 48, 2023
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